This proposal aims to characterize the function of the Hsp110 members of the heat shock protein family. Heat shock proteins (Hsps) are a large and important class of proteins which are expressed in response to cellular stress. The best characterized members are within Hsp70 family, which exhibit chaperone-like activity. The binding specificities of Hsps range from nonspecific binding of denatured proteins to specific targets within the cell such as steroid hormone receptors or cytoskeletal elements. The intracellular localization of these proteins is indicative of and vital to the function of these proteins. Hsp110 family is relatively new and uncharacterized class of Hsps. They are highly expressed in the cells of the Renal medulla where the cells exist under extreme osmotic stress, and thus must be important to the survival of the cells in this environment. The specific aims of this proposal are to 1) generate recombinant expression constructs of members of the Hsp110 family Hsp110, Hsp70RY and Osp94; 2) use these expressed recombinant proteins, as wee as the native Hsps to determine the chaperone activity of these Hsp110 family members; 3) determine the intracellular localization of the Hsp110 family members before stress upon heat or osmotic stress; and 4) identify major specific ligands for these members of the Hsp110 family. This project will enable me to develop a proficiency in mammalian biology, renal physiology and an expertise in stress protein biology.